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Trial registered on ANZCTR


Registration number
ACTRN12621000323820
Ethics application status
Approved
Date submitted
8/02/2021
Date registered
23/03/2021
Date last updated
29/10/2024
Date data sharing statement initially provided
23/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Virus-specific T cell therapy for transplant recipients
Scientific title
Phase I open-label clinical trial of allogeneic multi-virus-specific T cells for the treatment of viral complications in transplant recipients
Secondary ID [1] 303380 0
nil known
Universal Trial Number (UTN)
none
Trial acronym
none
Linked study record
none

Health condition
Health condition(s) or problem(s) studied:
Viral reactivation 320666 0
recurrent or drug-resistant viral infection 321180 0
Disease relating to cytomegalovirus 321181 0
Epstein–Barr virus 321182 0
BK polyomavirus 321183 0
Adenovirus. 321184 0
Condition category
Condition code
Infection 318508 318508 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The investigational product (IP) is ‘multi-virus-specific T cells TI1’, and consists of T cells targeting cytomegalovirus (CMV), Epstein–Barr virus (EBV), BK polyomavirus (BKV) and adenovirus (AdV). IP has previously been be generated in a good manufacturing practices (GMP) facility from the peripheral blood of healthy donors recruited via the Australian Bone Marrow Donor Registry. Batches of IP will be selected for participants based on human leukocyte antigen matching and virus specificity of the product. The safety of the IP in a therapeutic setting will be tested in 25 patients who have received a solid organ transplant (kidney, lung, heart, liver, or a combination of these). Participants will be recruited from Princess Alexandra Hospital, The Prince Charles Hospital, Royal Brisbane and Women’s Hospital and Royal Adelaide Hospital. Administration of the Investigational product will be reordered in the case report forms and records of use in the product accountability logs.

Four intravenous infusions of 4 × 10e7 cells suspended in clinical grade saline per infusion will be given; the second infusion will be 2 weeks after infusion one, to allow time to detect any immediate safety issues, and then infusions three and four will be delivered at 1-week intervals. At the Clinical Investigator’s discretion, the batch of T cells may be changed after two infusions. The IP will be administered intravenously over 5–10 min by a qualified person (e.g. registered nurse or clinician). This will be followed by a saline flush, which will take an additional 5–10 min.
Intervention code [1] 319695 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326469 0
The incidence of adverse events. Parameters collected include Abnormal laboratory findings and other abnormal assessments (eg vital signs observations etc) and participant-reported adverse events.
Timepoint [1] 326469 0
Adverse events will be collected at each visit commencing at the first infusion. Visit Infusions are weeks 2, 4, 5, 6, and follow-up visits approx. weeks 8, 12, 16, and 20.
Primary outcome [2] 326891 0
Clinically significant changes in laboratory tests. Blood tests will be haematology, biochemistry, and lymphocyte subsets
Timepoint [2] 326891 0
Blood Results will be collected at each visit commencing the first infusion. Visit infusion are week 2, 4, 5, 6 and follow up visits approx. week 8, 12, 16 and 20
Primary outcome [3] 326892 0
Clinically Significant Change in vital signs. This will include Blood pressure (via blood pressure cuff), heart rate and oxygen saturation (via a pulse oximeter), respiratory rate (by counting) and temperature (via a tympanic thermometer)
Timepoint [3] 326892 0
Vital signs will be measured weeks 2, 4, 5 and 6
Secondary outcome [1] 391595 0
The change in the proportion of functional virus-specific T cells, from prior to the first infusion to the first follow-up visit and at final follow-up.
Timepoint [1] 391595 0
Blood will be collected at each study visit (Baseline is immediately prior to infusion 1. and all infusions and follow-up visits) to allow the examination of peripheral blood mononuclear cells. These cells will be analysed to assess their phenotype and function over the course of the trial to determine any changes.

Eligibility
Key inclusion criteria
1. Aged 18 years or above
2. Previously received a solid organ transplant (kidney, lung, heart, liver, or a combination of these)
3. Viral infection or virus-induced neoplasia due to CMV, EBV, BKV or AdV, which is proven or suspected to be refractory to standard of care, or where standard of care is relatively or absolutely contraindicated.
4. Availability of a suitable batch of IP
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Significant non-malignant disease, e.g. severe cardiac or respiratory dysfunction
2. Uncontrolled psychosis, substance dependence, or any other psychiatric condition that may compromise the ability to participate in this trial
3. Prior cancers except: cancers with no evidence of disease recurrence and clinical expectation of recurrence of <5%; successfully treated non-melanoma skin cancer; localised prostate cancer; or carcinoma in situ of the cervix; or virus-induced neoplasia as specified in inclusion criterion 3.
4. Women who are pregnant, lactating or unwilling to use adequate contraception
5. Any other medical condition that, in the view of the Clinical Investigator, would prohibit participation

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As the IP is being tested in 25 participants, the study has a 95% probability of observing at least one participant experiencing an AE that is related to the IP if the probability of that event occurring is at least 11.3%, or affecting approximately 1 in 9 patients. Equivalent probabilities for observing AEs that affect 1 in 10 participants and 1 in 20 participants are 92.8% and 72.3% respectively.
Alternatively, the 95% confidence interval for the event rate would be (0%, 13.3%) if none of the 25 participants experience a particular AE, (4.0%, 19.5%) if 1 of 25 experience the AE, and (2.2%, 25.0%) if 2 of 25 experience the AE.
The primary endpoint of this study is safety. Safety endpoints will be presented descriptively, tabulating the number of patients with adverse events and the number of adverse events, overall and by system organ class (SOC) and preferred term (PT), including severity, duration, and relatedness. SAEs will be listed out separately and discussed individually. All adverse events will be listed.
The secondary endpoint is the within-participant change in the proportion of functional virus-specific T cells, from prior to the first infusion to the first follow-up visit and at final follow-up. With 25 participants, the study will have 90% power for an alpha=5% test to detect a difference in post-infusion versus pre-infusion levels of 0.68 standard deviations of the differences, and 80% power for 0.58 standard deviations.
The statistical distribution of this endpoint will be assessed via normal quantile plots. A log or logistic transformation will be applied to this variable if it leads to better conformity to a normal distribution. For the primary analysis, the difference of the endpoint at the first and the final follow-up visits and the baseline time point will be summarised with 95% confidence intervals. If a log transformation was applied, the results will be presented back transformed to yield post versus pre ratios. If no transformation was applied, the post versus pre differences will be presented.
To better understand the time course of the T cell responses, a within-subject analysis of responses across all infusions will be performed, with time modelled with a knotted spline to allow non-linear changes over time to be graphed, modelled and tested.
The statistical analysis plan will be finalised prior to data lock. If there is a substantial amount of missing, unused or spurious data, the primary analyses will be repeated to assess the robustness of the results. Differences from the intention-to-treat analysis will be investigated. Deviations from the statistical analysis plan will be documented in the clinical study repor

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/04/2021
Actual
31/05/2021
Date of last participant enrolment
Anticipated
5/05/2025
Actual
Date of last data collection
Anticipated
5/05/2026
Actual
Sample size
Target
25
Accrual to date
15
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 18637 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 18638 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 18639 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 23976 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 33007 0
4032 - Chermside
Recruitment postcode(s) [2] 33008 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 33009 0
5000 - Adelaide
Recruitment postcode(s) [4] 39464 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 307794 0
Government body
Name [1] 307794 0
National Health and Medical Research Council
Country [1] 307794 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Road
Herston
QLD
4006
Country
Australia
Secondary sponsor category [1] 308505 0
None
Name [1] 308505 0
Address [1] 308505 0
Country [1] 308505 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307809 0
QIMR Berghofer Human Research Ethics Committee
Ethics committee address [1] 307809 0
Ethics committee country [1] 307809 0
Australia
Date submitted for ethics approval [1] 307809 0
Approval date [1] 307809 0
19/11/2020
Ethics approval number [1] 307809 0
P3645

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108578 0
Prof Rajiv Khanna
Address 108578 0
QIMR Berghofer Centre for Immunotherapy and Vaccine Development, Tumour Immunology Laboratory
Level 10, CBCRC, QIMR Berghofer
300 Herston Rd
Herston QLD 4006
Country 108578 0
Australia
Phone 108578 0
+61 7 3362 0385
Fax 108578 0
Email 108578 0
Rajiv.Khanna@qimrberghofer.edu.au
Contact person for public queries
Name 108579 0
Michelle Neller
Address 108579 0
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Country 108579 0
Australia
Phone 108579 0
+61 7 33620412
Fax 108579 0
Email 108579 0
immunotherapy@qimrberghofer.edu.au
Contact person for scientific queries
Name 108580 0
Rajiv Khanna
Address 108580 0
QIMR Berghofer Centre for Immunotherapy and Vaccine Development, Tumour Immunology Laboratory
Level 10, CBCRC, QIMR Berghofer
300 Herston Rd
Herston QLD 4006
Country 108580 0
Australia
Phone 108580 0
+61 7 3362 0385
Fax 108580 0
Email 108580 0
Rajiv.Khanna@qimrberghofer.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.